Repeat controlled human malaria infection of healthy UK adults with blood-stage : Safety and parasite growth dynamics.

Unlabelled: In endemic settings it is known that natural malaria immunity is gradually acquired following repeated exposures. Here we sought to assess whether similar acquisition of blood-stage malaria immunity would occur following repeated parasite exposure by controlled human malaria infection (CHMI). We report the findings of repeat homologous blood-stage (3D7 clone) CHMI studies VAC063C (ClinicalTrials.

Inducible mechanisms of disease tolerance provide an alternative strategy of acquired immunity to malaria.

Immunity to malaria is often considered slow to develop but this only applies to defense mechanisms that function to eliminate parasites (resistance). In contrast, immunity to severe disease can be acquired quickly and without the need for improved pathogen control (tolerance). Using , we show that a single malaria episode is sufficient to induce host adaptations that can minimise inflammation, prevent tissue damage and avert endothelium activation, a hallmark of severe disease.

Mapping immune variation and gene switching in naive hosts infected with .

Falciparum malaria is clinically heterogeneous and the relative contribution of parasite and host in shaping disease severity remains unclear. We explored the interaction between inflammation and parasite variant surface antigen (VSA) expression, asking whether this relationship underpins the variation observed in controlled human malaria infection (CHMI). We uncovered marked heterogeneity in the host response to blood challenge; some volunteers remained quiescent, others triggered interferon-stimulated inflammation and some showed transcriptional evidence of myeloid cell suppression.

A Conserved TCRβ Signature Dominates a Highly Polyclonal T-Cell Expansion During the Acute Phase of a Murine Malaria Infection.

CD4 αβ T-cells are key mediators of the immune response to a first infection, undergoing extensive activation and splenic expansion during the acute phase of an infection. However, the clonality and clonal composition of this expansion has not previously been described. Using a comparative infection model, we sequenced the splenic CD4 T-cell receptor repertoires generated over the time-course of a infection.

An enhanced toolkit for the generation of knockout and marker-free fluorescent .

The rodent parasite is an important model of malaria. The ability to produce chronic infections makes it particularly useful for investigating the development of anti- immunity, as well as features associated with parasite virulence during both the acute and chronic phases of infection. also undergoes asexual maturation (schizogony) and erythrocyte invasion in culture, so offers an experimentally-amenable to model for studying gene function and drug activity during parasite replication.